Pharmacokinetics of epidural morphine and meperidine in humans

Five groups of surgical patients, each comprising six individuals, received epidural doses of morphine or meperidine, and the plasma and CSF kinetics were studied. Three groups received epidural doses of morphine 3 mg in 1 or 10 ml or meperidine 30 mg in 1 ml. Cerebrospinal fluid (CSF) and central venous blood opioid concentrations were measured intermittently for 6 h after injection. Two groups received epidural doses of morphine 3 mg in 1 ml or meperidine 30 mg in 1 ml, and opioid CSF concentrations were determined over a 24-h period. Morphine appeared rapidly in plasma, and maximum plasma concentrations were usually detected 5 min after injection and averaged 33 ng.ml-1 in the 1-ml volume group and 40 ng.ml-1 in the 10-ml volume group. The terminal plasma half-life averaged 91 +/- 34 min and 87 +/- 27 min, respectively (mean +/- SEM). Maximal plasma concentrations of meperidine were usually detected 10 or 15 min post-injection and averaged 196 +/- 29 ng.ml-1. The terminal plasma half-life averaged 124 +/- 26 min. Morphine crossed the dura relatively slowly, and the absorption half-life across the dura averaged 22 min. Maximal CSF concentrations were usually seen 60-90 min post-injection. In contrast, meperidine crossed the dura quickly, with an absorption half-life averaging 7.6 +/- 2.0 min. Maximal CSF concentrations were seen 15 or 30 min post-injection. Morphine and meperidine concentrations remained several times higher in the CSF than in the plasma. The fraction of the opioid dose crossing the dura was calculated to be 3.6% for morphine and 3.7% for meperidine. There were no significant differences in the kinetics of morphine administered in 1 or in 10 ml when CSF was sampled close to the site of lumbar epidural injection. The CSF concentration-time curves of both drugs decreased biexponentially after the initial rise due to diffusion across the dura. The early half-life in CSF averaged 73.3 +/- 11.5 min for morphine and 71.3 +/- 3.1 min for meperidine, and the late half-life averaged 369 +/- 113 min for morphine and 982 +/- 449 min for meperidine. Dose-normalized morphine and meperidine CSF concentrations after epidural administration showed that meperidine concentrations were down to one-fourth the corresponding morphine concentrations from the 2nd to the 15th h after administration, which may partly explain the longer duration of analgesia from morphine.(ABSTRACT TRUNCATED AT 400 WORDS)